Researchers at the Doherty Institute have developed a world-first technique for delivering mRNA into hard-to-reach resting CD4+ T cells, the immune cells where Human immunodeficiency virus (HIV) remains dormant, successfully ‘waking’ the virus.

Published on 29 May 2025 in Nature Communications, the study describes a new lipid nanoparticle formulation (‘LNP X’) that transfected more than 75 per cent of resting T cells without triggering toxicity or cell activation, enabling mRNA cargos to reverse HIV latency. 

HIV, the virus that causes acquired immunodeficiency syndrome (AIDS) remains uniquely difficult to cure. While all viruses hijack human cells to replicate, the body’s immune cells can typically identify and destroy the viral proteins. In contrast, HIV ‘hides’ in some cells without expressing any viral proteins and thus remains a lifelong disease. 

The Doherty Institute’s recent findings have discovered a way to flag silently infected cells. They have developed ‘lipid nanoparticles’, microscopic hollow oil droplets with genetic mRNA instructions within them, which merge with infected cells and instruct cells to search for HIV. While this technology does not kill infected cells and must be combined with other therapies before it can be offered to patients, it could expose the invisible virus. It is also unclear whether these lipid nanoparticles expose 100 per cent of infected cells, meaning some virus may still be able to evade detection and restart the infection. 

Researchers emphasise that the findings are preclinical, and further animal and human studies are necessary.  

Nevertheless, this finding offers hope to the 40 million people globally living with HIV that a permanent cure may one day be found.

The Peter Doherty Institute for Infection and Immunity is a joint venture between the University of Melbourne and the Royal Melbourne Hospital.